Methods of venting, sealing, and dispensing from a medicament container

ABSTRACT

A sealing assembly movable within an opening of a medicament container allows (1) gases to be vented from the container, (2) medication to be stored in the container, and (3) medication to be dispensed from the container. Methods of limiting exposure of the medication to oxygen to prevent degradation of the medication while in the medicament container are also disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 10/285,692,filed Nov. 1, 2002, now U.S. Pat. No. ______, which claims the benefitof U.S. Provisional Application No. 60/330,945, filed Nov. 2, 2001, andU.S. Provisional Application No. 60/350,972, filed Jan. 25, 2002. Thesedisclosures are each incorporated herein in their entirety by reference.

FIELD OF THE INVENTION

The present invention relates to medicament dispensing mechanisms foradministering a predetermined dosage of medication. In one embodiment,the present invention is directed to a medicament dispensing kit orinjector used for dispensing a gas sensitive medication (e.g.,dihydroergotamine (DHE) and epinephrine) that limits the exposure of themedication to the undesirable gas thereby improving and maintaining theeffectiveness of the medication over time. The present invention is alsodirected to methods of producing a kit that limits exposure of themedication to the undesirable gas (e.g., oxygen). The present inventionis further directed to a method of storing a medicament in anautoinjector for prolonged periods, and then administering themedicament contained therein.

BACKGROUND OF THE INVENTION

Migraine headaches or migraines are generally described as recurrentsevere headaches, which can be disabling to the sufferer. The durationof migraines can last up to seventy-two (72) hours and can beaccompanied by nausea, vomiting and sensitivity to light. It isgenerally agreed that to successfully treat a migraine, concentrationsof an anti-migraine drug in the bloodstream must reach a therapeuticlevel within a certain time from the onset of the migraine headache inorder to be effective in reducing and/or eliminating the migraineheadache. DHE is effective for the treatment of migraines. DHE can beadministered intramuscularly, subcutaneously, as a nasal spray, or byother delivery routes.

DHE (as with other medicaments), however, degrades when exposed tooxygen. To be effective, the dissolved oxygen content needs to bemaintained below at least 2 ppm and more preferably around 0.5 ppm. Atpresent, DHE is only available in ampoules for injection using a manualsyringe or for use in a nasal spray. The ampoules protect the medicationfrom oxygen exposure while stored within the ampoule. The use ofampoules, however, requires the user to carryout a number ofmanipulations prior to use including breaking open the ampoule in orderto either draw the medication into a syringe or inserting the openedampoule into a nasal spray for use. Breaking the ampoule may behazardous because it may produce shards of glass or particles that maymix with the medication and be injected or inhaled by the migrainesufferer. While the ampoule is open and prior to insertion in either thesyringe or the nasal sprayer, the DHE is exposed to oxygen, which canlead to degradation of the DHE. Furthermore, DHE is often selfadministered by the migraine sufferer. Self administration occurs whilethe sufferer may be experiencing reduced functional and concentrationabilities. As such, the sufferer may improperly administer the correctdosage of medication or take an over or under dosage of the medication.

There is a need for a safe and effective method of storing andadministering medicaments, such as DHE, that protects against oxygendegradation and allows a migraine sufferer to self administer apredetermined dosage of medication.

OBJECTS OF THE INVENTION

It is therefore an object of the present invention to provide apackaging system for medication that minimizes exposure to oxygen whilepermitting easy self administering.

It is another object of the present invention to provide a packagingsystem for medication that limits degradation of the medication.

It is another object of the present invention provide a medicamentdispensing kit that provides for the stable storage of a dose of anoxygen sensitive medicament (e.g., DHE or epinephrine).

It is another object of the present invention to provide a medicamentdispensing kit that minimizes the exposure of a dose of DHE to oxygen.

It is another object of the present invention to provide a medicamentdispensing assembly that does not require the use of an ampoule to storethe medication.

It is another object of the present invention to provide a single usemedicament dispensing kit that enables a user to self administer a doseof medication.

It is yet another object of the present invention to provide a packagingassembly that stores a single dose of medication in a protectiveenvironment.

It is yet another object of the present invention to provide a packagingsystem that extends the shelf life of the medicament.

It is another object of the present invention to provide secondarypackaging to prevent puncturing or damage to the oxygen barrier.

Additional objects and advantages of the invention are set forth, inpart, in the description which follows, and, in part, will be apparentto one of ordinary skill in the art from the description and/or practiceof the invention.

SUMMARY OF THE INVENTION

In response to the foregoing challenges, applicants have developed aninnovative medicament container, medicament dispensing kit and packagingprocess that minimizes exposure of the medication to oxygen to preventdegradation of the medication.

The present invention is directed to a medicament dispensing kit foradministering a predetermined dose of medication. It is contemplatedthat the medicament dispensing kit may be used by an individual for selfmedication and/or treatment. It is further contemplated that themedicament dispensing kit may be used by a health care professional toadminister a predetermined dose of medication for a patient. Inaccordance with the present invention, each medicament dispensing kitincludes a predetermined dose of medication. The predetermined dose ofmedication may include DHE. The invention, however, is not limited tothe use of DHE; rather, other oxygen sensitive medications includingepinephrine or medications that degrade with prolonged exposure tooxygen or other undesirable gases are contemplated for use and areconsidered to be within the realm of the present invention. It is alsocontemplated to use the present invention in connection with the storageof medications for the purpose of increasing shelf life. As such, it iscontemplated that the present invention may be used in connection withany medicament that is stored for prolonged periods of time.

In accordance with the present invention, the predetermined dose ofmedication is stored in a medicament container, which was filled in aninert gas environment, which may be provided in an isolator, a tunnel,through a flush of inert gas or a shower of inert gas. The medicamentcontainer includes a cartridge assembly, which receives thepredetermined dose of medication. The cartridge assembly may be formedfrom glass or another suitable material. The cartridge assembly has atleast one opening formed therein to facilitate filling and dispensing ofthe dose of medication. Each opening contains at least one sealingassembly. It is contemplated that the sealing assemblies may be formedfrom a rubber or other material that functions as an oxygen absorbingmaterial or an oxygen barrier material. It is also contemplated that onesealing assembly may be formed from an absorbing material and anothersealing assembly may be formed from a barrier material. It is furthercontemplated that one or more of the sealing assemblies may be formedfrom an oxygen permeable material, whereby the oxygen absorbing materialmay withdraw oxygen from the system through the seal. One of the sealingassemblies is movable within the interior portion of the cartridgeassembly in response to activation of a dispensing assembly tofacilitate the dispensing of the dose of medication. This sealingassembly is positioned within the interior portion of the containerprior to filling with the dose of medication.

Another sealing assembly is located in another opening in the cartridgeassembly after the cartridge assembly is filled with the dose ofmedication. This sealing assembly may include a venting assembly forventing the inert gas from an interior of the cartridge assembly afterthe predetermined dose of medication has been located therein. The inertgas is removed under vacuum pressure. It is also contemplated that it isnot necessary to remove all of the inert gas within the cartridgeassembly. A partial vacuum may be used to remove a portion of the gas.The sealing assembly moves from a sealing position to a dispensingposition in response to activation of the dispensing assembly.Alternatively, the sealing assembly may be placed over the neck portionof the cartridge assembly. The sealing assembly is punctured in responseto actuation of the dispensing assembly and more particularly movementof a needle assembly. The sealing assembly is punctured by the needleassembly. Alternatively, it is contemplated to provided a diaphragmsealing assembly, wherein the diaphragm is ruptured in response toincreased pressure by the medicament in response to activation of thedispensing assembly.

In accordance with the present invention, the medicament container mayfurther include a dispensing element for administering the predetermineddose of medication from the medicament container in response toactivation of the dispensing assembly. In the case of an auto-injectoror a syringe, the dispensing element may be a needle for injecting thepredetermined dose of medication into the user upon activation of thedispensing assembly.

The kit in accordance with the present invention further includes adispensing assembly adapted to receive the medicament container therein.The dispensing assembly dispenses the predetermined dose of medicationupon activation by a user. The dispensing assembly may be anauto-injector, a syringe, a nasal sprayer, a needle free auto-injectoror other drug delivery system. The dispensing assembly is stored in asealed package. The sealed package forms an oxygen barrier to preventoxygen from penetrating the dispensing assembly to degrade the dose ofmedication. In accordance with the present invention, the sealed packageis a high barrier pouch, which prevents oxygen from entering theinterior of the package. Preferably, the high barrier pouch is alaminated pouch having several layers. Furthermore, one of the layers ispreferably a layer of an aluminum foil. It is contemplated that the highbarrier pouch may be located within a rigid secondary packaging such asa rigid container or tube to prevent puncture of the barrier pouch. Itis also contemplated that the sealed package may be formed as a rigidcontainer or formed from an oxygen barrier material such as aluminum ora suitable polymer. It is also contemplated that the sealed package maybe a thermoformed package or a metal tube.

An inert gas is flushed through the interior compartment of the sealedpackage when the dispensing assembly is placed in the package to removethe presence of any oxygen or undesired gas within the compartment. Agas absorbing material may be located in the sealed package to absorbany oxygen that may be out gassed from the dispensing assembly. It iscontemplated that ascorbic acid, iron powder, borohydride ormordenite/calcium oxide systems or halon gas or equivalent materials maybe used as a gas absorbing material. It is also contemplated that a gasabsorbing material be omitted from the package. It is also contemplatedthat the interior compartment of the sealed package may be filled withan inert gas or air. It is further contemplated that the interiorcompartment may be sealed under vacuum to create a vacuum within thesealed package. This will limit the amount of air or gas within thesealed package at the onset. It is contemplated that a certain amount ofair will permeate the seal of the package and be absorbed by theabsorbing material. The presence of the vacuum will increase the usefullife of the gas absorbing material by limiting the exposure of thematerial to the undesired gas at the onset.

The present invention is not limited to a single sealed package; rather,it is contemplated that the sealed package may include a plurality ofseparate sealed interior compartments. Each sealed compartment containsa dispensing assembly having the predetermined dose of medicationlocated therein.

The present invention is also directed to a method of packaging apredetermined dose of medication. The packaging method reduces exposureof the medication to oxygen, which reduces degradation of themedication. The method includes providing a predetermined dose ofmedication, which is placed in a medicament container. The filling ofthe medicament container occurs in an environment containing an inertgas. The use of the inert gas (e.g., argon, nitrogen, CO₂ or halon)limits oxygen exposure. During the filling operation, the interiorcompartment of the medicament container is purged using the inert gas toeliminate the presence of oxygen.

The medicament container is then sealed in the inert gas environment,which may be provided by an isolator, a tunnel, through a flush of inertgas or a shower of inert gas. During the sealing operation, a sealingassembly is placed in an opening in the medicament container. Thesealing assembly is located within the opening such that it is in aventing position to permit the removal of any remaining gas frommedicament container. It is also contemplated that a portion of theinert gas may remain within the medicament container. A partial vacuummay be created within the container using the inert gas. The inert gasis then withdrawn from the medicament container by applying a vacuum tothe medicament container. It is also contemplated that all of the inertgas, a portion of the inert gas, or none of the inert gas is removedfrom the medicament container. The sealing assembly is then seated inthe opening to a sealing position, while the medicament container isstill subject to the vacuum. Alternatively, the sealing assembly may beplaced around the neck portion of the cartridge assembly after the inertgas purge. The sealing assembly may include a portion that fits withinthe neck portion and a portion that extends around the neck portion ofthe cartridge assembly.

The medicament container is then placed in a dispensing assembly. Themedicament container is positioned in the dispensing assembly such thatthe user can simply activate the dispensing assembly to dispense thepredetermined dosage of the medication. As discussed above, it iscontemplated that dispensing assembly may be a syringe, anauto-injector, a nasal sprayer, or other suitable means for dispensingthe predetermined dosage.

The loaded dispensing assembly is then located in a package. Prior toand during the locating of the dispensing assembly in the package, theinterior of the package may be flushed with an inert gas to remove anyoxygen. An oxygen absorbing material is located within the package. Theoxygen absorbing material may be formed on the wall of the package,inserted as a separate packet within the package, or provided as apowder within the interior of the package, formed as part of one of thecomponents of the drug delivery system (e.g. a component of theautoinjector), located in a compartment within the drug delivery system,or a separate component of the drug delivery system. The package may befilled with an inert gas to prevent shrinkage of the pouch created bythe absence of air within the pouch. As discussed above, the package isdesigned to limit exposure of the medication to oxygen. Furthermore, thepackaging and the packaging process are designed to limit oxygenexposure and absorb any oxygen that may be out gassed from thedispensing assembly once located in the package.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in conjunction with the followingdrawing in which like reference numerals designate like elements andwherein:

FIG. 1 is a cross sectional schematic view of a medicament dispensingkit in accordance with an embodiment of the present invention;

FIG. 2 is a cross sectional schematic view illustrating the sealingassemblies and the container assembly for the medicament container;

FIG. 3 is a cross sectional schematic view illustrating the location ofthe sealing assemblies and the container assembly during the ventingoperation whereby the inert gas is vented from the interior of thecontainer assembly;

FIG. 4 is a cross sectional schematic view illustrating the location ofthe sealing assemblies and the container assembly in the sealed positionafter the venting operation;

FIG. 5 is a cross sectional view of the sealing assembly for themedicament container in accordance with the present invention;

FIG. 6 is a cross sectional view of the medicament containerillustrating the position of the sealing assembly in a storage positionwhen the dispenser assembly is located in the sealed package;

FIG. 7 is a cross sectional view of the medicament containerillustrating the position of the sealing assembly upon activation of thedispenser assembly by the user;

FIG. 8 is a cross sectional view of the medicament containerillustrating the position of the sealing assembly in an ejectionposition whereby the medication is administered to the patient;

FIG. 9 is a cross sectional view of the medicament container inaccordance with another embodiment of the present invention;

FIG. 10 is a cross sectional view of the medicament container of FIG. 9located within a syringe;

FIG. 11 is a cross sectional view of the medicament container of FIG. 9located in an auto-injector;

FIG. 12 is a cross sectional view of the sealing assembly of FIG. 9; and

FIG. 13 is a cross sectional view of a medicament dispensing kit havinga cartrix type dispensing assembly in accordance with an embodiment ofthe present invention.

DETAILED DESCRIPTION OF THE INVENTION

A medicament dispensing kit 1 is illustrated in FIG. 1. The kit 1includes a sealed package 10, a medication dispensing assembly 20, and amedicament container 30. The kit 1 also includes an oxygen absorbingcomponent 40.

The medicament container 30 will now be described in greater detail inconnection with FIGS. 2-8. The medicament container 30 includes acartridge assembly or vial 31 having an interior compartment forreceiving a predetermined dose of medication. The cartridge assembly orvial 31 is preferably formed from glass. The present invention, however,is not limited to a cartridge assembly 31 formed from glass; rather,other materials that are non reactive with DHE or other oxygen sensitivemedicaments and prevent the passage of oxygen there through areconsidered to be well within the scope of the present invention. Themedicament container 30 also includes a pair of sealing assemblies 32and 33 for sealing the open end portions of the cartridge assembly 31 asshown in FIG. 4. The sealing assemblies 32 and 33 are preferably formedfrom rubber. It is contemplated that the sealing assemblies 32 and 33may be formed from a material (e.g., rubber or other suitable material)that has oxygen barrier capabilities (e.g., West 4405/50 or 4416/50bromobutyl rubber) or oxygen absorbing capabilities (e.g., Diakyo 777series rubber or PTFE). It is further contemplated that either of thesealing assemblies 32 and 33 may be formed from an oxygen permeablematerial to permit the passage of oxygen from the interior of themedicament container 30 to the oxygen or gas absorbing material. It isalso contemplated that the medicament container 30 may be formed from anoxygen or gas permeable material to permit the withdrawal of oxygen orother undesirable gas from the interior of the medicament container 30by the oxygen/gas absorbing material.

A first sealing assembly 32 is positioned in the interior compartment ofthe cartridge assembly 31, as shown in FIG. 2. The first sealingassembly 32 is adapted to frictionally engage the inner surface of thecartridge assembly 31 to prevent the medication from passing between thefirst sealing assembly 32 and the inner surface of the cartridgeassembly 31. The first sealing assembly 32 is adapted to be engaged byan actuator element of the dispensing assembly 20, as shown in FIG. 1.Under the action of the dispensing assembly 20, the first sealingassembly 32 slides within the interior compartment of the cartridgeassembly 31 towards the second sealing component 33, as shown in FIGS.6-8. The movement of the first sealing assembly 32 pressurizes themedication within the cartridge assembly 31 to dislodge the secondsealing component 33 to permit the administering of the medication. Themedication may be administered through a dispensing element 34, as shownin FIGS. 1 and 6-8. The dispensing element 34 includes a housing 341that is adapted to engage a neck portion 311 of the cartridge assembly31. The dispensing element 34 also includes a needle assembly 342 forinjecting the medication directly into the bloodstream, skin tissue, ormuscle tissue. The needle assembly 342 may be used when the dispensingassembly 20 is an auto-injector, a syringe, or an alternative drugdelivery system. The present invention, however, is not limited to theuse of a needle assembly 342; rather, the aspirating element may beprovided to permit aspiration of the medication such that it can bedispensed through a nasal sprayer, needle free auto-injector, oralternative drug delivery system.

The second sealing component 33 is illustrated in greater detail in FIG.5. Like the first sealing assembly 32, the second sealing component 33includes a body portion 331 that is designed to frictionally engage theinner surface of the cartridge assembly 31 adjacent the neck portion311. The second sealing component 33 further includes one or moreventing passageways 332 formed in a portion of the exterior surface ofthe body portion 331. As described in greater detail below, the ventingpassageways 332 permit the venting of gases from the interiorcompartment of cartridge assembly 31 during the filling operation, asshown in FIG. 3. The venting passageways 332 further permit the passageof medication there through during the medication dispensing operation,as shown in FIG. 8. The body portion 331 of the second sealing component33 includes a plurality of ribs or projections 333 extending from an endportion, as shown in FIG. 5. The ribs 333 are radially spaced around theperimeter of the second sealing component 33. During the dispensingoperation, the second sealing component 33 moves from the positionillustrated in FIG. 6 to the position illustrated in FIG. 8 whereby theribs 333 of the second sealing component 33 contact an interior surfaceof the housing 341. The venting passageways 332 permit the passage ofmedication into the housing 341. The medication then travels through thespace between the ribs 333 and interior surface of the housing 341 tothe needle assembly 342. The space between the ribs 333 and interiorsurface of the housing 341 ensures a liquid communication path betweenthe cartridge assembly 31 and the needle assembly. This space may alsocontrol the size of medication particles traveling through the needleassembly 342 to prevent clogging of the needle assembly 342.

The medicament container 30 is adapted to be received within adispensing assembly 20. In accordance with one embodiment of the presentinvention, the dispensing assembly 20 is an auto-injector, as shown inFIG. 1. It is contemplated that the medicament container 30 may be usedin a wide variety of single use auto-injectors as disclosed, for examplebut not limited to, in U.S. Pat. No. 4,031,893 to Kaplan et al., U.S.Pat. No. 5,295,965 to Wilmot et al., U.S. Pat. No. 5,102,393 to Sarnoffet al., and U.S. Pat. No. 5,092,843 to Monroe et al. The disclosures ofeach of these patents are specifically incorporated herein by reference.It is also contemplated that the medicament container 30 may be used ina multi-use auto-injector as disclosed, for example in, U.S. Pat. No.5,085,642 to Sarnoff et al. The disclosure of this patent isspecifically incorporated herein by reference. The present invention,however, is not limited to an auto-injector; rather other dispensingassemblies including but not limited to prefilled syringes, nasalsprayers, needle free auto-injectors and other medication administeringdevices are considered to be well within the scope of the presentinvention.

The auto-injector 20 illustrated in FIG. 1 includes a housing 21. Themedicament container 30 is located within the housing 21. Theauto-injector 20 further includes an operating assembly 22 locatedwithin the housing 21. The operating assembly 22 includes an actuatorarm 221, which is adapted to engage the first sealing assembly 32. Uponactuation of the operating assembly 22, the biased actuator arm 221moves the first sealing assembly 32 from the storage positionillustrated in FIG. 6 through the dispensing position illustrated inFIG. 7 to the position illustrated in FIG. 8. The pressure within theinterior compartment of the cartridge assembly 31 causes the secondsealing component 33 to move to an extended position, as shown in FIG.8, such that the dose of medication can be dispensed through thedispensing element 34.

The dispensing assembly 20 and the medicament container 30 are packagedin a sealed package 10. The sealed barrier package 10 prevents oxygenfrom entering the interior of the package 11 through the package walls12. The package walls 12 are preferably formed as a laminate containingmore than one layer. For example, each wall 12 of the package 10preferably includes a layer of aluminum foil. The wall 12 may be formedwith three laminate layers including polyethylene terephthalate (PET),aluminum foil and polyethylene (PE). Alternatively, the wall 12 may beformed with five laminate layers including biaxial nylon, polyvinyldichloride (PVDC), low density polyethylene (LDPE), aluminum foil,another layer of LDPE and linear, low density polyethylene (LLDPE). Thepresent invention is not limited to the above-described laminatedlayers. Various combinations of these materials are possible and arecontemplated to be within the scope of the present invention providedthese combinations provide a barrier to oxygen penetration. Thelaminated walls 12 form a package 10 having an interior compartment 11.The above-described dispensing assembly 20 containing the medicamentcontainer 30 are located within the compartment 11 prior to sealing thepackage 10. The package 10 can be sealed by any suitable means thatwould prevent the passage of oxygen into the interior compartment 11. Toprotect the package 10 from inadvertent rupture, the package 10 may belocated in a rigid secondary package 90. It is also contemplated thatthe package 10 may be formed as a rigid container (such as for example acan) using aluminum or other suitable oxygen barrier materials. It isfurther contemplated that the package 10 may be thermoformed or formedas a rigid tube.

To absorb any oxygen that may be present in the interior compartment 11,that may infiltrate the package 10 at the seal between, for example, thelaminate layers or that may be out gassed from the dispensing assembly20, an oxygen absorbing material 40 is located within the interiorcompartment. Ascorbic acid, iron powder, borohydride ormordenite/calcium oxide systems, or halon gas are all suitable oxygenabsorbing materials. The oxygen absorbing material may be applied to theinterior wall of the walls 12. A package 40 of the material may belocated within the package 10, as shown in FIG. 10. Alternatively, thematerial may be placed in powder form within the compartment 11. Theoxygen absorbing material may take the form of a self adhesive patch ordisc 80 sewed to an inner wall of the package 10. It is alsocontemplated that one or more of the components of the dispensingassembly 20 may be formed from the oxygen absorbing material. It is alsocontemplated, but not preferred, that the interior compartment 11 may beevacuated of all gas so that a gas absorbing component is unnecessary.

Packaging the dispensing assembly 20 into a high barrier laminatepackage 10 preferable incorporating aluminum foil with an oxygenabsorber and preferably an inert gas flush will provide a very goodoxygen barrier to prevent ingress of oxygen into the pouch. The oxygenabsorber will absorb any oxygen that maybe present in the pouch, in thedispensing assembly 20 and the medicament container 30, dissolved oxygenthat may out gas from the assembly 20 and the container 30 and inparticular the sealing assemblies 32 and 33. The absorber 40 will act asan oxygen sink to draw any extraneous oxygen out of the container 30. Itis contemplated that a sufficient amount of the oxygen absorber will beprovided to absorb any oxygen that permeates in through the seals in thepackage 10 over the expected lifetime of the product.

A variation of the medicament container 30 will be described inconnection with FIG. 9. The medicament container 300 includes acartridge assembly 31, as discussed above. A first sealing assembly 32is located within the interior of the cartridge assembly 31. The sealingassembly 31 is adapted to engaged by the actuator assembly 51 of asyringe 50, as shown in FIG. 10, or the actuator assembly 61 of theauto-injector 60, as shown in FIG. 11. The medicament container 300 doesnot include a second assembly 33 that is received in an opening of thecartridge assembly 31. Instead, a sealing assembly 310 is provided. Thesealing assembly 310 includes an inner sealing member 320, which isformed from a rubber material, as described above. As shown in FIG. 12,the sealing assembly 310 further includes an outer sealing member 330formed as a metal cap assembly. The outer sealing member has a holeformed therein to permit the passage of the needle assembly 521 or 621therethrough. A foil layer 331 may be provided to cover the hole priorto passage of the needle assembly 521 or 621 therethrough to prevent thepassage of oxygen into the inner compartment 11. It is contemplated thatthe foil layer 331 may be positioned on the outer surface of the outersealing member 330 or between the outer sealing member 330 and the innersealing member 320. The outer sealing member is adapted to be crimped,screw fit or compression fit onto the neck portion of the cartridgeassembly 31. The outer sealing member 330 provides an axial seal. Theinner sealing member 320 provides an inner radial seal in the opening inthe neck portion of the cartridge assembly 31. The second sealingassembly 310 is adapted to engage the outer surface and the innersurface of the neck portion of the cartridge assembly 31, as shown inFIG. 9. The outer sealing member 330 may be formed as a foil sheet thatis laminated onto the top surface of the inner sealing member 320. Thefoil may be pierceable by the needle or an end of the actuator assembly.The foil is not intended to contact the medication. It is alsocontemplated that a reducing die could be used to push the sealingassembly into the cartridge assembly 31 without the use of vacuumpressure. It is also contemplated that a foil layer may be provided onthe surface of the plunger 32.

A dispensing element 52 is adapted to engage the outer surface of thecartridge assembly 31 such that the sealing assembly 310 is sandwichedthere between, as shown in FIG. 10. During operation, the actuatorassembly 51 moves the first sealing assembly 32 within the interiorcompartment of the cartridge assembly 31. The pressure supplied by theuser causes the needle assembly 521 to move towards the sealing assembly310. In response, the sealing assembly 310 contacts an end portion of aneedle assembly 521 in the dispensing element 52, which causes theneedle assembly 521 to penetrate the inner sealing member 320. The doseof medication then passes through the needle assembly 521. For a syringetype dispensing element, the needle assembly 521 punctures the sealbefore the actuator assembly 51 is depressed. For a cartrix typedispensing assembly illustrated in FIG. 13, the diaphragm 600 expandsand is ruptured after the actuator assembly has been actuated.

It is also contemplated that the present invention may be used inconnection with a Hypak® syringe. With this arrangement, the needleassembly 342 is bonded or attached directly to the end of the cartridgeassembly. The needle assembly 342 is located within a hole within thecartridge assembly, which preferably formed from glass. As such, thehousing 341 can be eliminated. Furthermore, only one sealing assembly incontact with the medicament is necessary. An additional seal may beprovided around the outer periphery of the needle assembly.

A dispensing element 62 is adapted to engage the outer surface of thecartridge assembly 31 such that the sealing assembly 310 is sandwichedthere between, as shown in FIG. 11. During operation, the actuatorassembly 61 moves the first sealing assembly 32 within the interiorcompartment of the cartridge assembly 31. In response, the cartridgeassembly 31 and the sealing assembly 310 move within the dispensingassembly 60 in the direction of the needle assembly 621 in thedispensing element 62. After injection of the needle assembly 621 intothe user, the end portion of the needle assembly 621 located within thedispensing assembly 60 penetrates the sealing assembly 310 such that themedication is then transmitted through the needle assembly 621 into theuser. The operation of the needle assembly 621 penetrating a sealingassembly 310 is described in greater detail in U.S. Pat. No. 6,210,369to Wilmot et al., the disclosure of which is hereby specificallyincorporated herein by reference. The dose of medication then passesthrough the needle assembly 621. It is preferably that the inner sealingassembly 320 extend into the neck portion of the cartridge assembly 31to provide a radial seal and increased protection against oxygenpenetration. It, however, is contemplated that the size the innersealing member 320 that projects into the opening of the neck portionmay be reduced or eliminated, as shown for example in FIG. 9. This,however, may result in increased oxygen penetration.

The packaging process will now be described. The packaging methodreduces exposure of the medication to oxygen. Thus, reducing degradationof the medication. The method includes providing a predetermined dose ofmedication, which is placed in a medicament container 30. The filling ofthe medicament container 30 occurs in an environment containing an inertgas. The inert gas may be located in an isolator, a tube or tunnelcontaining a flush of inert gas or a shower of inert gas. The use of theinert gas (e.g., argon or nitrogen), which is heavier than oxygen,reduces oxygen exposure. During the filling operation, the interiorcompartment of the cartridge assembly 31 is purged using the inert gasto eliminate the presence of oxygen. It is also contemplated that thecartridge assembly 31 may be filled from either open end.

The cartridge assembly 31 is then sealed in the inert gas environment.During the sealing operation, the sealing assembly 33 is placed in anopening in the cartridge assembly 31, as shown in FIG. 3. The sealingassembly 33 is located within the opening such that it is in a ventingposition to permit the removal of any remaining gas from the interiorcompartment of the cartridge assembly 31. The inert gas is thenwithdrawn from the cartridge assembly 31 by applying a vacuum. It is notnecessary to remove all of the inert gas. The sealing assembly 33 isthen seated in the opening to a sealing position by the application ofpressure to the sealing assembly 33 while the medicament container 30 isstill subject to the vacuum. It is also contemplated that a reducing diecould be used to push the sealing assembly into the cartridge assembly31 without the use of vacuum pressure. The venting operation is notperformed when the sealing assembly 310 is used.

The medicament container 30 is then placed in a dispensing assembly 20.The medicament container 30 is positioned in the dispensing assembly 20such that the user can simply activate the operating assembly 22 ofdispensing assembly 20, as shown for example in FIG. 1, to dispense thepredetermined dosage of the medication. As discussed above, it iscontemplated that dispensing assembly 20 may be a syringe, as shown inFIG. 10, an auto-injector, as shown in FIGS. 1 and 11, a nasal sprayeror other suitable means for dispensing the predetermined dosage. It isalso contemplated that the dispensing assembly 20 may be more tightlysealed to prevent the passage of oxygen or gas if the gas absorbingmaterial is located within the assembly 20.

In one embodiment, the gas absorbing material 40 is a separate memberthat is stored within a space within the autoinjector housing 21, and ingaseous communication with the medicament cartridge assembly. In suchembodiment, it may be desirable (though not required) to manufacturecomponents of the dispensing assembly 20 itself substantially imperviousto air to shield the gas absorbing material 40 from air. In thisembodiment, the outer package 12 can be dispensed with.

The loaded dispensing assembly 20 is then located in a package 10. Priorto and during the locating of the dispensing assembly 20 in the package10, the interior of the package 10 is flushed with an inert gas toremove any oxygen. It is not necessary to perform this operation, but itis preferable because it reduces the stress on the oxygen absorbingmaterial thereby permitting the material to Withdraw more oxygen fromthe components. An oxygen absorbing material 40 is located within thepackage 10. The oxygen absorbing material 40 may be formed on the wallof the package, inserted as a separate packet, as shown in FIG. 1 withinthe package or powder within the interior of the package or as part ofthe dispensing assembly 20. As discussed above, the package 10 isdesigned to limit exposure of the medication to oxygen. Furthermore, thepackaging 10 and the packaging process are designed to limit oxygenexposure and absorb any oxygen that may be out gassed from thedispensing assembly 20 once located in the package 10. The containers 11are filled in an argon or inert gas environment, may be inspected andpackaged in air as quickly as possible to minimize the exposure of themedicament to oxygen or other undesired gases. The inert gas environmentmay be provided by means of an isolator, a tunnel, through a flush ofinert gas or a shower of inert gas

The above described medicament container, kit and packaging processsimplify the use of DHE and other oxygen sensitive medications, whileimproving the stability of DHE. Furthermore, the dispensing assembly 20provides for standard easier use allowing immediate easy use by thepatient without significant manipulation or assembly. The dispensingassembly 20 will be user friendly, more convenient & provide betterdosing accuracy over an ampoule based system. This is particularlyimportant for the migraine application during patient self-injectionwhen patient's functional and concentration abilities are reduced, theirvision maybe impaired & they maybe feeling nausea. It will be apparentto those skilled in the art that various modifications and variationsmay be made without departing from the scope of the present invention.Although the present invention has been described in connection with thetreatment of migraines using DHE, it is contemplated that variousmedications including epinephrine may be employed while practicing thepresent invention. Furthermore, a single package 10 has been described.It is contemplated, however, that each package 10 may include aplurality of interior compartments 11 that may be separately opened.Each compartment may contain a dispensing assembly 20 and a medicamentcontainer 30. Alternatively, one compartment may contain a dispensingassembly and a medicament container, while the remaining compartmentscontain additional doses of medication in medicament containers 30 thatare loaded into the dispensing assembly by the patient or health careprovider when opened. Thus, it is intended that the present inventioncovers the modifications and variations of the invention, provided theycome within the scope of the appended claims and their equivalents.

1. A method of storing and dispensing a dose of medication, the methodcomprising: filling a medicament container with a dose of medication;positioning a sealing assembly in an open end of the medicamentcontainer at a first position to allow any gases from the medicamentcontainer to vent through a passageway in the sealing assembly tooutside the medicament container; positioning the sealing assembly at asecond position in the open end of the medicament container to seal thedose of medication in the medicament container; placing the medicamentcontainer in a dispensing assembly; and positioning the sealing assemblyat the first position to allow the dose of medication to pass throughthe passageway to the dispensing assembly during a dispensing operation.2. The method of claim 1 wherein prior to filling the medicamentcontainer with a dose of medication, the method further comprisespurging the medicament container with an inert gas.
 3. The method ofclaim 1 wherein placing the medicament container in a dispensingassembly comprises placing the medicament container in a syringe, anautomatic injector, or a nasal sprayer.
 4. The method of claim 1 whereinprior to positioning the sealing assembly at the second position, themethod further comprises applying a vacuum to the medicament containerwhile the sealing assembly is at the first position to withdraw anygases from the medicament container.
 5. The method of claim 1 furthercomprising placing a gas absorbing material in the dispensing assembly.6. The method of claim 1 wherein after placing the medicament containerin a dispensing assembly and prior to positioning the sealing assemblyat the first position, the method further comprises: placing thedispensing assembly in a package; and sealing the package to limitexposure of the dispensing assembly to oxygen.
 7. The method of claim 6wherein sealing the package comprises sealing the package under vacuumto create a vacuum within the sealed package to limit exposure of thedispensing assembly to oxygen.
 8. The method of claim 6 wherein prior toplacing the dispensing assembly in a package, the method furthercomprises flushing the package with an inert gas.
 9. The method of claim6 wherein prior to sealing the package, the method further comprisesinserting or attaching an oxygen absorbing material in the package. 10.A method of storing and dispensing a dose of medication, the methodcomprising: filling a medicament container with a dose of medication;venting any gases present in the medicament container via a passagewayformed in a sealing assembly positioned in an open end of the medicamentcontainer; sealing the dose of medication in the medicament containerwith the sealing assembly; placing the medicament container in adispensing assembly; and passing the dose of medication from themedicament container into the dispensing assembly via the passagewayformed in the sealing assembly.
 11. The method of claim 10 whereinfilling a medicament container comprises filling a medicament containerhaving a neck portion with a dose of medication.
 12. The method of claim11 wherein venting any gases comprises venting any gases present in themedicament container via a passageway formed in a sealing assemblyinserted into an open end of the neck portion of the medicamentcontainer.
 13. The method of claim 10 wherein prior to passing the doseof medication, the method further comprises creating a pressure in themedicament container to move the sealing assembly to a dispensingposition.
 14. The method of claim 10 wherein passing the dose ofmedication comprises creating a pressure to force the dose of medicationfrom the medicament container into the dispensing assembly via thepassageway formed in the sealing assembly.
 15. A method of storing anddispensing a dose of medication, the method comprising: filling amedicament container with a dose of medication; forming a sealingassembly having a first end and a second end, the second end having aplurality of ribs or projections extending therefrom; positioning thesealing assembly in an open end of the medicament container to allowgases to vent from the medicament container; positioning the sealingassembly in the open end of the medicament container to seal the dose ofmedication in the medicament container; placing the medicament containerin a dispensing assembly; and positioning the sealing assembly in theopen end of the medicament container such that the ribs or projectionscontact an interior surface of the dispensing assembly to allow the doseof medication to flow out from the container into the dispensingassembly through a space created between the ribs or projections and theinterior surface of the dispensing assembly.
 16. The method of claim 15wherein the respective positions to allow gases to vent from themedicament container and to allow the dose of medication to flow outfrom the container are the same position.
 17. The method of claim 15wherein forming a sealing assembly further comprises forming a sealingassembly having an exterior surface between the first and second ends,the exterior surface having a passageway formed therein extending fromthe first end toward the second end, the passageway operable to ventthere through gases from the container during a container fillingoperation and operable to pass there through the dose of medication fromthe container during a medication dispensing operation.
 18. The methodof claim 15 further comprising creating a pressure to position thesealing assembly such that the ribs or projections contact an interiorsurface of the dispensing assembly
 19. The method of claim 15 furthercomprising creating a pressure to force the dose of medication to flowout from the container.
 20. The method of claim 15 wherein positioningthe sealing assembly in an open end of the medicament containercomprises frictionally engaging an inner surface of the medicamentcontainer with the sealing assembly.